Host interaction with neoplastic cells, the basis of surveillance mechanism, involves complex immunologic and nonimmunologic responses. Protease pathways directly recruited at the inflammatory sites by the tumor or elicited by immune responses to the tumor play a significant and central role in the pathobiology of neoplasia and may regulate cellular migration and metastasis and the generation of biologically active derivaties that orchestrate the inflammatory response. This program will address the immunologic recruitment of exrinsic protease pathways as well as the activation of these pathways by tumor cells directly. Thus, the major focus will be the particiption of the coagulation and fibrinolytic pathways in the pathobiology of neoplasia. Projects will address immune responses to tumor specific antigens in which T cells initiate and regulate protease activating mechanisms on part of monocytes and macrophages. Cellular immune pathways of the immune response to tumors will be examined using cloned specific T cells and the biological significance of T cell intructed macrophage pathways will be explored in experimental models in vivo. The role of plasma protease pathways in the mediation of tumor killing by host responses will be characterized and the significance in vivo delineated. The direct oranganization of coagulation and fibrinolytic pathways on tumor and immune cells will be biochemically quantitated and characterized in an attempt to arrive at a precise understanding of local proteolytic events in the tumor microenvironment.